Randomized Phase III Study of Sequential Radiochemotherapy of Anaplastic Glioma With PCV or Temozolomide (NOA-04)

Neuro-Oncology Working Group of the German Cancer Society

Status and phase: Completed; Phase 3

Conditions: Oligodendroglioma; Oligoastrocytoma; Anaplastic Astrocytoma

Treatments: Radiation: Focal radiotherapy; Drug: Temozolomide

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT00717210

NOA-04

Details and patient eligibility

About

Background: The optimal treatment of anaplastic gliomas is controversial. Standard of care in most centers is still radiotherapy. This phase III study compared the efficacy and safety of radiotherapy vs chemotherapy in patients (pts) with newly-diagnosed, supratentorial gliomas of WHO grade III.

Methods: Pts were randomized 2:1:1 between June 1999 and February 2005 in 34 German centers to receive (i) a 6-week course of radiotherapy (1,8-2 Gy fractions, total dose 54-60 Gy) or (ii) four 6-week cycles of CCNU at 110 mg mg/m2 on day 1, vincristine at 2 mg on days 8 and 29 and procarbazine at 60 mg/m2 on days 8-21 or eight 4-week cycles of 200 mg/m2 temozolomide on days 1-5. Treatment was stopped prematurely at disease progression or occurrence of unacceptable toxicity. At this time or at disease progression, treatment in the radiotherapy group was continued with one of the chemotherapies (1:1 randomization) and with radiotherapy in both chemotherapy groups. The primary endpoint was time-to-treatment-failure (TTF) defined as progression after radiotherapy and one chemotherapy in either sequence, or any time before if further therapy could not be employed. Assuming a 50% improvement in TTF of starting with chemotherapy, 318 pts were to be enrolled to provide 80% power to achieve statistical significance at a one-sided level of 0.05.

Enrollment: 318 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• written informed consent
• centrally confirmed anaplastic glioma according to the WHO-classification 1998/2000
• age ≥ 18 years
• Karnofsky performance status (KPS) of 70 or higher
• no prior systemic chemotherapy or radiation therapy of the brain
• no HIV infection
• adequate bone marrow reserve, liver function, and renal function
• Patients on corticosteroids had to be on a stable or decreasing dosage within the 14 days prior to randomization

Exclusion criteria

• Glioblastoma
• infratentorial localization of the tumor
• pregnancy or lactation period
• serious medical or neurological comorbidity
• additional malignancy requiring radio- or chemotherapy
• known hypersensitivity against study drugs
• inability to swallow
• frequent emesis
• psychological. familial, sociological or geographical situations impairing compliance with F/U examinations
• parallel participation in other studies

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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318 participants in 2 patient groups

A

Active Comparator group

Description:

Conventional Radiotherapy

Treatment:

Radiation: Focal radiotherapy

B1/2

Experimental group

Description:

1:1 randomization between temozolomide and procarbazine/lomustine/vincristine (PCV)

Treatment:

Drug: Temozolomide